Rosiglitazone Improves Stallion Sperm Motility, ATP Content, and Mitochondrial Function.
Abstract: Media used for equine sperm storage often contain relatively high concentrations of glucose, even though stallion spermatozoa preferentially utilize oxidative phosphorylation (OXPHOS) over glycolysis to generate ATP and support motility. Rosiglitazone is an antidiabetic compound that enhances metabolic flexibility and glucose utilization in various cell types, but its effects on sperm metabolism are unknown. This study investigated the effects of rosiglitazone on stallion sperm function in vitro, along with the possible role of AMP-activated protein kinase (AMPK) in mediating these effects. Spermatozoa were incubated with or without rosiglitazone, GW9662 (an antagonist of peroxisome proliferator-activating receptor-gamma), and compound C (CC; an AMPK inhibitor). Sperm motility, viability, reactive oxygen species production, mitochondrial membrane potential (mMP), ATP content, and glucose uptake capacity were measured. Samples incubated with rosiglitazone displayed significantly higher motility, percentage of cells with normal mMP, ATP content, and glucose uptake capacity, while sperm viability was unaffected. The percentage of spermatozoa positive for mitochondrial ROS was also significantly lower in rosiglitazone-treated samples. AMPK localized to the sperm midpiece, and its phosphorylation, was increased in rosiglitazone-treated spermatozoa. CC decreased sperm AMPK phosphorylation and reduced sperm motility, and successfully inhibited the effects of rosiglitazone. Inclusion of rosiglitazone in a room temperature sperm storage medium maintained sperm motility above 60% for 6 days, attaining significantly higher motility than sperm stored in control media. The ability of rosiglitazone to substantially alleviate the time-dependent deterioration of stallion spermatozoa by diverting metabolism away from OXPHOS and toward glycolysis has novel implications for the long-term, functional preservation of these cells.
© 2016 by the Society for the Study of Reproduction, Inc.
Publication Date: 2016-09-28 PubMed ID: 27683266DOI: 10.1095/biolreprod.116.142687Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article explores how rosiglitazone, an antidiabetic drug, can enhance the motility and function of stallion sperm in vitro, potentially improving long-term preservation. The drug’s effect may be mediated by AMP-activated protein kinase, a cellular energy regulator.
Research Goal and Methodology
- The researchers aimed to understand the impact of rosiglitazone on the function of stallion sperm, given that the current process of sperm storage media contains high glucose concentrations while stallion spermatozoa primarily utilizes oxidative phosphorylation (OXPHOS) not glycolysis to generate ATP (the source of energy in cells) and support its functionality.
- They conducted in vitro studies where they exposed the stallion spermatozoa to various conditions including different chemical substances such as rosiglitazone, GW9662 (an antagonist of peroxisome proliferator-activating receptor-gamma), and compound C (an AMPK inhibitor).
Observations and Findings
- The sperm samples incubated with rosiglitazone showed a significant increase in motility, ATP content, and glucose uptake capacity. Additionally, a higher percentage of cells showed normal mitochondrial membrane potential (mMP).
- The viability of the spermatozoa remained unaffected despite the rosiglitazone treatment. Further, the presence of mitochondrial ROS (Reactive Oxygen Species) was significantly lower compared to the untreated samples.
- Upon evaluation, it was found that AMPK, a potential mediator in delivering the effects of rosiglitazone, was present in the midpiece of the spermatozoa. Also, the phosphorylation of AMPK was found to increase in rosiglitazone-treated spermatozoa, suggestive of enhanced energy regulation.
Role of AMPK
- Compound C, an AMPK inhibitor, was found to reduce the sperm motility and AMPK phosphorylation, further demonstrating the essential role of AMPK in the functionality and energy regulation of spermatozoa.
- This evidence also indicates that the effects of rosiglitazone on enhancing sperm functionality are potentially facilitated by the action of AMPK.
Long-term Effects
- The study found that rosiglitazone maintained sperm motility above 60% for up to 6 days in room temperature storage, surpassing the motility of the sperm stored in control media.
- The researchers concluded that rosiglitazone helps divert the metabolic activity of spermatozoa away from oxidative phosphorylation (OXPHOS) towards glycolysis, thus pacifying time-dependent deterioration and ensued implications for the long-term functional preservation of stallion spermatozoa.
Cite This Article
APA
Swegen A, Lambourne SR, Aitken RJ, Gibb Z.
(2016).
Rosiglitazone Improves Stallion Sperm Motility, ATP Content, and Mitochondrial Function.
Biol Reprod, 95(5), 107.
https://doi.org/10.1095/biolreprod.116.142687 Publication
Researcher Affiliations
- Priority Research Centre in Reproductive Science, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia aleona.swegen@uon.edu.au.
- Priority Research Centre in Reproductive Science, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
- Priority Research Centre in Reproductive Science, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
- Priority Research Centre in Reproductive Science, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
MeSH Terms
- AMP-Activated Protein Kinases / metabolism
- Adenosine Triphosphate / metabolism
- Animals
- Glycolysis / drug effects
- Horses
- Hypoglycemic Agents / pharmacology
- Male
- Membrane Potential, Mitochondrial / drug effects
- Mitochondria / drug effects
- Mitochondria / metabolism
- Phosphorylation / drug effects
- Reactive Oxygen Species / metabolism
- Rosiglitazone
- Semen Analysis / veterinary
- Sperm Motility / drug effects
- Spermatozoa / drug effects
- Spermatozoa / metabolism
- Thiazolidinediones / pharmacology
Citations
This article has been cited 14 times.- Jurado-Campos A, Soria-Meneses PJ, Arenas-Moreira M, Alonso-Moreno C, Rodríguez-Robledo V, Soler AJ, Garde JJ, Del Rocío Fernández-Santos M. Minimizing sperm oxidative stress using nanotechnology for breeding programs in rams.. J Anim Sci Biotechnol 2023 Aug 10;14(1):106.
- Liu Q, Zhu C, Ma Y, Wang Y, Zheng L, Jin T, He S, Yang F, Dong W. Metformin improves fish sperm quality by regulating glucose uptake capacity during in vitro storage.. J Anim Sci 2023 Jan 3;101.
- Bucci D, Spinaci M, Bustamante-Filho IC, Nesci S. The sperm mitochondria: clues and challenges.. Anim Reprod 2022;19(4):e20220131.
- Cheng Q, Li L, Jiang M, Liu B, Xian Y, Liu S, Liu X, Zhao W, Li F. Extend the Survival of Human Sperm In Vitro in Non-Freezing Conditions: Damage Mechanisms, Preservation Technologies, and Clinical Applications.. Cells 2022 Sep 12;11(18).
- Mehdipour M, Daghigh-Kia H, Najafi A, Mehdipour Z, Mohammadi H. Protective effect of rosiglitazone on microscopic and oxidative stress parameters of ram sperm after freeze-thawing.. Sci Rep 2022 Aug 17;12(1):13981.
- Mu Y, Yin TL, Zhang Y, Yang J, Wu YT. Diet-induced obesity impairs spermatogenesis: the critical role of NLRP3 in Sertoli cells.. Inflamm Regen 2022 Aug 2;42(1):24.
- Wang Y, Zhang L, Sohail T, Kang Y, Sun X, Li Y. Chlorogenic Acid Improves Quality of Chilled Ram Sperm by Mitigating Oxidative Stress.. Animals (Basel) 2022 Jan 11;12(2).
- Bazzano M, Laus F, Spaterna A, Marchegiani A. Use of nutraceuticals in the stallion: Effects on semen quality and preservation.. Reprod Domest Anim 2021 Jul;56(7):951-957.
- Aitken RJ, Baker MA. The Role of Genetics and Oxidative Stress in the Etiology of Male Infertility-A Unifying Hypothesis?. Front Endocrinol (Lausanne) 2020;11:581838.
- Li RN, Zhu ZD, Zheng Y, Lv YH, Tian XE, Wu D, Wang YJ, Zeng WX. Metformin improves boar sperm quality via 5'-AMP-activated protein kinase-mediated energy metabolism in vitro.. Zool Res 2020 Sep 18;41(5):527-538.
- Peña FJ, O'Flaherty C, Ortiz Rodríguez JM, Martín Cano FE, Gaitskell-Phillips GL, Gil MC, Ortega Ferrusola C. Redox Regulation and Oxidative Stress: The Particular Case of the Stallion Spermatozoa.. Antioxidants (Basel) 2019 Nov 19;8(11).
- Ortiz-Rodriguez JM, Balao da Silva C, Masot J, Redondo E, Gazquez A, Tapia JA, Gil C, Ortega-Ferrusola C, Peña FJ. Rosiglitazone in the thawing medium improves mitochondrial function in stallion spermatozoa through regulating Akt phosphorylation and reduction of caspase 3.. PLoS One 2019;14(7):e0211994.
- Thuwanut P, Comizzoli P, Pruksananonda K, Chatdarong K, Songsasen N. Activation of adenosine monophosphate-activated protein kinase (AMPK) enhances energy metabolism, motility, and fertilizing ability of cryopreserved spermatozoa in domestic cat model.. J Assist Reprod Genet 2019 Jul;36(7):1401-1412.
- Martin-Hidalgo D, Hurtado de Llera A, Calle-Guisado V, Gonzalez-Fernandez L, Garcia-Marin L, Bragado MJ. AMPK Function in Mammalian Spermatozoa.. Int J Mol Sci 2018 Oct 23;19(11).
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
